Long-term Phase 3 data show treatment with REMICADE achieves clinical response
HORSHAM, Pa., and KENILWORTH, N.J., December 8, 2005 – Landmark studies published today in The New England Journal of Medicine demonstrate the benefits of treatment with REMICADE (infliximab) in patients with ulcerative colitis (UC).
At week 8, in both the 54-week ACT 1 trial and the 30-week ACT 2 trial, statistically significant differences in the proportion of patients in clinical response, clinical remission, and with mucosal healing were shown in UC patients treated with REMICADE versus those receiving placebo. In particular, approximately two-thirds of UC patients treated with REMICADE achieved the primary endpoint of clinical response, defined as improvement in signs and symptoms. Moreover, more than half had mucosal healing and more than one-third were in clinical remission. Furthermore, in both ACT 1 and ACT 2, nearly one-quarter of REMICADE patients receiving corticosteroids at baseline were in remission and steroid-free by week 30. In both ACT 1 and ACT 2, a significantly greater proportion of patients treated with REMICADE compared with placebo achieved clinical response, clinical remission, and mucosal healing from week 8 through the end of each trial (week 54 in ACT 1 and week 30 in ACT 2).
A major advance in the treatment of UC, REMICADE is the first and only biologic indicated in the United States for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately-to-severely active UC who have had an inadequate response to conventional therapy. This approval was based on the 30-week data from both trials.
"These long term results highlight the benefits of REMICADE for the treatment of UC," said William J. Sandborn, MD, professor of medicine, Mayo Clinic College of Medicine, head of the Inflammatory Bowel Disease (IBD) Interest Group, director of the IBD Clinical Research Unit at Mayo Medical Center, and lead study investigator. "These data demonstrate that many patients treated with REMICADE experienced not only a reduction in symptoms but had remission of their colitis and mucosal healing, findings that support a new therapeutic approach and standard of care for physicians and their UC patients."
UC is a chronic disease affecting more than 1.2 million people in the U.S. and Europe for whom there is no medical cure. Currently, there are no other biologic therapies approved to treat moderate to severe UC. Characterized by inflammation and ulceration of the inner lining of the colon, UC symptoms can often include weight loss, severe – sometimes uncontrollable – bloody diarrhea, fatigue, and frequent abdominal pain. Alternative treatments are limited and, if conventional treatments do not control the progression of the disease, many patients may have to face surgical removal of the colon.
"Achieving and maintaining improvements over time are challenging goals in the treatment of ulcerative colitis, particularly in patients that do not respond to conventional medications such as steroids," said Paul Rutgeerts, MD, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium, and lead investigator of the ACT 1 study. "REMICADE has, for several years, demonstrated efficacy in the treatment of Crohn's disease, and now has proven its ability to be an effective therapy for patients with ulcerative colitis, for which there are limited treatment options."
The efficacy of REMICADE in the treatment of inflammatory bowel disease is well established in adults. First approved in 1998 for Crohn's disease (CD), REMICADE remains the only anti-tumor necrosis factor (TNF-alpha) therapy indicated for the treatment of moderately to severely active CD in patients who have had an inadequate response to conventional therapy. Recently, REMICADE also became the only biologic approved by the US Food and Drug Administration (FDA) for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately-to-severely active UC who have had an inadequate response to conventional therapy.
About ACT 1 and ACT 2
ACT 1 and ACT 2 were multicenter, Phase 3, randomized, double-blind, placebo-controlled, clinical trials conducted to evaluate the safety and efficacy of REMICADE for the treatment of patients with moderately-to-severely active UC who experienced an inadequate response to conventional therapy. A total of 728 patients with active UC who were unresponsive to at least one standard therapy, including corticosteroids, other immunosuppressants, or 5-ASAs, were enrolled in ACT 1 (n=364) and ACT 2 (n=364). Patients in ACT 1 and ACT 2 had endoscopic evidence of moderate or severe UC (total Mayo score of 6 to12) and an endoscopy score greater than or equal to 2. ACT 1 patients received treatment with placebo or REMICADE 5 mg/kg or REMICADE 10 mg/kg at weeks 0, 2, and 6 and then every eight weeks through week 46 and had their last evaluation at week 54. ACT 2 patients received treatment with placebo or REMICADE 5 mg/kg or REMICADE 10 mg/kg at weeks 0, 2, and 6 and then every eight weeks through week 22 and had their last evaluation at week 30.
In ACT 1, at week 8, 69 percent of patients in the REMICADE 5 mg/kg group and 62 percent of patients in the REMICADE 10 mg/kg group were in clinical response, compared with 37 percent of patients in the placebo group (P < 0.001 for both comparisons). In ACT 2, at week 8, 65 percent of patients in the REMICADE 5 mg/kg group and 69 percent of patients in the REMICADE 10 mg/kg group were in clinical response compared with 29 percent of patients in the placebo group (P < 0.001 for both comparisons).
In both studies, the proportions of patients who achieved clinical response or clinical remission at weeks eight and 30 in ACT 1 and ACT 2 and week 54 in ACT 1 were significantly greater among patients treated with REMICADE 5 mg/kg and 10 mg/kg than placebo-treated patients (P less than or equal to 0.003 for all comparisons with placebo). The rates of clinical response were similar between the corticosteroid-refractory and corticosteroid-responsive subgroups. The proportions of patients with sustained clinical response or sustained clinical remission were significantly higher in each REMICADE group than in the placebo group (P less than or equal to 0.002 for all comparisons with placebo). Additionally, the proportion of patients treated with REMICADE 5 mg/kg and 10 mg/kg who achieved mucosal healing at weeks 8 and 30 (in ACT 1 and ACT 2) and at week 54 (in ACT 1) was significantly greater than that for the placebo-treated patients (P less than or equal to 0.009 for all comparisons with placebo).
Furthermore, 61 percent of the patients in ACT 1 and 51 percent of the patients in ACT 2 were receiving corticosteroids at baseline. The baseline median daily corticosteroid dose was 20 mg/day in both studies. Of the patients who were receiving corticosteroids at baseline, the proportion of patients who were in clinical remission and had discontinued corticosteroids was significantly greater in the 5 mg/kg REMICADE group versus the placebo group at week 30 (P = 0.030 for ACT 1 and P = 0.010 for ACT 2); and at week 54 (P = 0.006 for ACT 1), an important factor for patients with UC who may experience considerable morbidity as a result of corticosteroids.
The serious adverse events reported in these trials were similar to those reported in previous REMICADE clinical trials. See Important Safety Information below.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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